CN106699749A - Application of 5-piperonyl thiazole derivative as anticancer drug - Google Patents
Application of 5-piperonyl thiazole derivative as anticancer drug Download PDFInfo
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Abstract
The invention relates to application of a 5-piperonyl thiazole derivative as shown in the chemical structural formula I or salt thereof in the preparation of an anticancer drug. in the chemical structural formula I, R is selected from C1-C2 alkyl, C3-C4 linear alkyl or C3-C4 branched alkyl; X1 and X5 are selected from hydrogen, deuterium, C1-C2 alkyl, fluorine, chlorine, bromine or nitro; X2 and X4 are selected from hydrogen, deuterium, C1-C2 alkyl, fluorine, chlorine, bromine, nitro or trifluoromethyl; and X3 is selected from hydrogen, deuterium, C1-C2 alkyl, methoxy, ethoxy, fluorine, chlorine, bromine, nitro, ethoxyformyl or trifluoromethyl. The salt is selected from hydrochloride, hydrobromide, sulfate, nitrate, phosphate, mesylate, benzene sulfonate, p-toluene sulfonate, malate, lactate, succinate, maleate or fumarate.
Description
Technical field
The present invention relates to the new application of compound, specifically application of the 5- piperonyls thiazole in cancer therapy drug is prepared.
Background technology
Chinese invention patent [CN 104530035A, on April 22nd, 2015 is open] describes 5- piperonyl -4- alkyl -2-
The application of fragrant amino thiazole or its salt in anti-disinfectant use in agriculture and insecticide is prepared.Hu Aixi etc. describes 5- benzyls
- 4- alkyl -2- fragrant aminos thiazole and its salt in cancer therapy drug is prepared application [SCI, 2013,
34(7)：1646~1652；Chinese invention patent CN 102070556B, on March 20th, 2013 authorizes；Chinese invention
Patent CN 102319244A, on January 18th, 2012 is open].
The content of the invention
Anticancer is being prepared it is an object of the invention to provide the 5- piperonyls thiazole shown in chemical structural formula I or its salt
Application in medicine：
Wherein, R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl；X1、X5It is selected from：Hydrogen,
Deuterium, C1~C2Alkyl, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, fluorine, chlorine, bromine,
Nitro or trifluoromethyl；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, methoxyl group, ethyoxyl, fluorine, chlorine, bromine, nitro,
Ethoxycarbonyl or trifluoromethyl；The salt is selected from：Hydrochloride, hydrobromate, sulfate, nitrate, phosphate, first
Sulfonate, benzene sulfonate, tosilate, malate, lactate, succinate, maleate or fumarate.
It is selected from object of the present invention is to provide 5- piperonyl thiazoles：5- piperonyl -4- the tert-butyl groups -2- (3- methylbenzenes
Amino) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (2- fluoroanilinos) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (4- Fluoroanilines
Base) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (2- chloroanilinos) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (3- chloroanilinos)
Thiazole, 5- the piperonyl -4- tert-butyl groups -2- (4- chloroanilinos) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (3- bromoanilinos) thiophene
Azoles, 5- the piperonyl -4- tert-butyl groups -2- (4- bromoanilinos) thiazole, the 5- piperonyl -4- tert-butyl groups -2- [3- (trifluoromethyl) benzene
Amino] thiazole, the 5- piperonyl -4- tert-butyl groups -2- [4- (trifluoromethyl) phenylamino] thiazole, the 5- piperonyl -4- tert-butyl group -2- (4-
Methoxybenzene amino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (4- nitrobenzene amino) thiazole, the 5- piperonyl -4- tert-butyl groups -2-
(4- ethoxycarbonyls phenylamino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (3,4- dichloro-benzenes amino) thiazole, 5- piperonyls
- 4- the tert-butyl groups -2- (3,5- dichloro-benzenes amino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (the fluoro- 3- chloroanilinos of 4-) thiazoles or
5- piperonyl -4- the tert-butyl groups -2- [3,5- bis- (trifluoromethyl) phenylamino] thiazole.
The present invention has the following advantages that compared with prior art：
5- piperonyls thiazole or its salt have good active anticancer.
Specific embodiment
Following examples are intended to illustrate rather than limitation of the invention further.
Embodiment 1
The preparation of 5- piperonyl -4- tert-butyl groups -2- (2- methylphenylaminos) thiazole
The bromo- propiones of 2mmol 2,2- dimethyl -5- (3,4- methylene-dioxy) -4-, 2mmol 2- aminomethyl phenyl thiocarbamides,
15mL acetone, flow back 8h, and reaction solution adjusts pH7 with ammoniacal liquor, and column chromatography obtains the yellow oil 5- piperonyl -4- tert-butyl groups
- 2- (2- methylphenylaminos) thiazole, yield 60.4%.1H NMR(CDCl3, 400MHz) and δ：1.45 (s, 9H,
3×CH3), 2.34 (s, 3H, CH3), 4.06 (s, 2H, CH2), 5.94 (s, 2H, OCH2O), 6.62~6.75
(m, 3H, C6H3), 7.01~7.26 (m, 4H, C6H4)。
Embodiment 2
The preparation of 5- piperonyl -4- tert-butyl groups -2- (3- methylphenylaminos) thiazole
Preparation method reacts 8h with embodiment 1, obtains the yellow oil 5- piperonyl -4- tert-butyl groups -2- (3- methyl phenylaminos
Base) thiazole, yield 65.4%.1H NMR(CDCl3, 400MHz) and δ：1.45 (s, 9H, 3 × CH3), 2.33
(s, 3H, CH3), 4.08 (s, 2H, CH2), 5.96 (s, 2H, OCH2O), 6.64~6.77 (m, 3H, C6H3),
6.91 (d, J=7.6Hz, 1H, C6H44-H), 7.07 (d, J=7.6Hz, 2H, C6H46-H), 7.08 (s, 1H,
C6H42-H), 7.22 (t, J=8Hz, 1H, C6H45-H)。
Embodiment 3
The preparation of 5- piperonyl -4- tert-butyl groups -2- (3- bromoanilinos) thiazole
Preparation method reacts 6h with embodiment 1, obtains the yellow oil 5- piperonyl -4- tert-butyl groups -2- (3- bromoanilinos)
Thiazole, yield 48.9%；1H NMR(CDCl3, 400MHz) and δ：1.41 (s, 9H, 3 × CH3), 4.11 (s,
2H, CH2), 5.95 (s, 2H, OCH2O), 6.65~6.76 (m, 3H, C6H3), 7.12~7.23 (m, 3H,
C6H44,5,6-H), 7.60 (s, 1H, C6H42-H)。
Embodiment 4
The preparation of 5- piperonyl -4- tert-butyl groups -2- (4- bromoanilinos) thiazole
Preparation method reacts 6h with embodiment 1, obtains the yellow solid 5- piperonyl -4- tert-butyl groups -2- (4- bromoanilinos)
Thiazole, yield 51.1%, m.p.118~120 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.41 (s, 9H, 3 × CH3),
4.10 (s, 2H, CH2), 5.95 (s, 2H, OCH2O), 6.65~6.76 (m, 3H, C6H3), 7.22 (d, J=8.8
Hz, 2H, C6H42,6-H), 7.40 (d, J=8.8Hz, 2H, C6H43,5-H).
Embodiment 5
The preparation of the 5- piperonyl -4- tert-butyl groups -2- [4- (trifluoromethyl) phenylamino] thiazole
Preparation method reacts 6h with embodiment 1, obtains the yellow oil 5- piperonyl -4- tert-butyl groups -2- [4- (trifluoromethyl)
Phenylamino] thiazole, yield 74.5%,；1H NMR(CDCl3, 400MHz) and δ：1.43 (s, 9H, 3 × CH3),
4.12 (s, 2H, CH2), 5.96 (s, 2H, OCH2O), 6.66~6.77 (m, 3H, C6H3), 7.42 (d, J=8.4
Hz 2H, C6H42,6-H), 7.56 (d, J=8.4Hz, 2H, C6H43,5-H).
Embodiment 6
The preparation of the 5- piperonyl -4- tert-butyl groups -2- (4- methoxybenzenes amino) thiazole
The bromo- propiones of 2mmol 2,2- dimethyl -5- (3,4- methylene-dioxy) -4-, 2mmol 4- methoxyphenyl thiocarbamides,
15mL ethanol, flowed back 8h, and reaction solution adjusts pH7 with ammoniacal liquor, boils off partial solvent, freezes crystallization, and filtering is dried,
Obtain yellow solid the 5- piperonyl -4- tert-butyl groups -2- (4- methoxybenzenes amino) thiazole, yield 27.0%, m.p.147.0~149.0
℃；1H NMR(CDCl3, 400MHz) and δ：1.34 (s, 9H, 3 × CH3), 3.73 (s, 3H, OCH3), 4.05
(s, 2H, CH2), 5.98 (s, 2H, OCH2O), 6.67 (d, J=8Hz, 1H, C6H35-H), 6.75 (s,
1H, C6H32-H), 6.84 (d, J=8Hz, 1H, C6H36-H), 7.22 (d, J=8.4Hz, 2H, C6H43,
5-H), 7.47 (d, J=8.4Hz, 2H, C6H42,6-H), 9.48 (s, 1H, NH).
Embodiment 7
The preparation of the 5- piperonyl -4- tert-butyl groups -2- (4- ethoxycarbonyls phenylamino) thiazole
Preparation method reacts 6h with embodiment 6, obtains the beige solid 5- piperonyl -4- tert-butyl groups -2- (4- ethoxycarbonyls
Phenylamino) thiazole, yield 75.3%, m.p.177~180 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.38 (t,
J=7.2Hz, 3H, CH3), 1.44 (s, 9H, 3 × CH3), 4.12 (s, 2H, CH2), 4.35 (q, J=7.2Hz,
2H, OCH2), 5.96 (s, 2H, OCH2O), 6.67 (d, J=8Hz, 1H, C6H35-H), 6.69 (s, 1H,
C6H32-H), 6.76 (d, J=8Hz, 1H, C6H36-H), 7.34 (d, J=8.8Hz, 2H, C6H42,6-H),
8.01 (d, J=8.8Hz, 2H, C6H43,5-H).
Embodiment 8
The preparation of the 5- piperonyl -4- tert-butyl groups -2- (3,4- dichloro-benzenes amino) thiazole
Preparation method reacts 8h with embodiment 1, obtains the yellow solid 5- piperonyl -4- tert-butyl groups -2- (3,4- diChloroanilines
Base) thiazole, yield 69.0%, m.p.124~126 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.41 (s, 9H,
3×CH3), 4.11 (s, 2H, CH2), 5.95 (s, 2H, OCH2O), 6.65~6.76 (m, 3H, C6H3), 1.55
(dd, J1=8.4Hz, J2=2.8Hz, ClC6H36-H), 7.33 (d, J=8.4Hz, 1H, ClC6H35-H),
7.63 (d, J=2.8Hz, ClC6H32-H)。
Embodiment 9
The preparation of the 5- piperonyl -4- tert-butyl groups -2- (3,5- dichloro-benzenes amino) thiazole
Preparation method reacts 8h with embodiment 1, obtains the yellow solid 5- piperonyl -4- tert-butyl groups -2- (3,5- diChloroanilines
Base) thiazole, yield 64.4%, m.p.99~101 DEG C；1H NMR (400MHz, CDCl3)δ：1.41 (s, 9H,
3×CH3), 4.12 (s, 2H, CH2), 5.95 (s, 2H, OCH2O), 6.65~6.76 (m, 3H, C6H3), 6.96
(t, J=1.6Hz, 1H, ClC6H34-H), 7.34 (d, J=1.6Hz, 2H, ClC6H32,6-H).
Embodiment 10
The preparation of the 5- piperonyl -4- tert-butyl groups -2- (the fluoro- 3- chloroanilinos of 4-) thiazole
Preparation method reacts 8h with embodiment 1, obtains the yellow solid 5- piperonyl -4- tert-butyl groups -2- (the fluoro- 3- chlorobenzenes ammonia of 4-
Base) thiazole, yield 77.4%, m.p.100~102 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.51 (s, 9H,
3×CH3), 4.07 (s, 2H, CH2), 5.98 (s, 2H, OCH2O), 6.63~6.79 (m, 3H, C6H3), 7.15~7.40
(m, 3H, FC6H3)。
Embodiment 11
The preparation of 5- piperonyls thiazole (I) and its salt
Wherein R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl；X1、X5It is selected from：Hydrogen, deuterium,
C1~C2Alkyl, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, fluorine, chlorine, bromine, nitro
Or trifluoromethyl；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, methoxyl group, ethyoxyl, fluorine, chlorine, bromine, nitro, ethoxy
Formoxyl or trifluoromethyl.The salt is selected from：Hydrochloride, hydrobromate, sulfate, nitrate, phosphate, methanesulfonic acid
Salt, benzene sulfonate, tosilate, malate, lactate, succinate, maleate or fumarate.
5- piperonyl thiazoles are prepared by Chinese invention patent [CN104530035A, 2015.4.22 are disclosed] method
(Ⅰ)。
Wherein, the 5- piperonyls -4- tert-butyl groups -2- (2- fluoroanilinos) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (4- Fluoroanilines
Base) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (2- chloroanilinos) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (3- chloroanilinos)
Thiazole, 5- the piperonyl -4- tert-butyl groups -2- (4- chloroanilinos) thiazole, the 5- piperonyl -4- tert-butyl groups -2- [3- (trifluoromethyl)
Phenylamino] thiazole, the 5- piperonyl -4- tert-butyl groups -2- (4- nitrobenzene amino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (3,4-
Dimethyl benzene amino) thiazole and the 5- piperonyl -4- tert-butyl groups -2- [3,5- bis- (trifluoromethyl) phenylamino] thiazoles and its salt presses
It is prepared by Chinese invention patent [CN104530035A] method.Chinese invention patent [CN104530035A] discloses these changes
The physical property and spectral data of compound.
Embodiment 12
5- piperonyls thiazole and its antitumor activity of salt
1. antitumor activity principle
Mtt assay biological activity test, also known as MTT colorimetric methods, is a kind of method for detecting cell survival and growth.MTT
Analytic approach is with living cells metabolin reducing agent tetrazolium bromide [3- (4,5- dimethyl -2- thiazoles) -2,5- diphenyl bromination tetrazoles；3-
(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, MTT] based on.MTT is a kind of energy
Receive the dyestuff of hydrogen atom.The dehydrogenase related to NADP can turn the MTT of yellow in the cell in living cells mitochondria
The first a ceremonial jade-ladle, used in libation (formazon) of insoluble bluish violet is melted into, and dead cell is then without this function.Formazon is dissolved with DMSO
Afterwards, OD value is determined with ELIASA under certain wavelength, can both quantifies the survival rate for measuring cell.According to OD value
Inhibitory action of the change observation sample to tumour cell.
2. antitumor activity experiment
Sample：5- piperonyls thiazole (I) and its salt.
Wherein R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl；X1、X5It is selected from：Hydrogen, deuterium,
C1~C2Alkyl, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, fluorine, chlorine, bromine, nitro
Or trifluoromethyl；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, methoxyl group, ethyoxyl, fluorine, chlorine, bromine, nitro, ethoxy
Formoxyl or trifluoromethyl.
The salt is selected from：Hydrochloride, hydrobromate, sulfate, nitrate, phosphate, mesylate, benzene sulfonate,
Tosilate, malate, lactate, succinate, maleate or fumarate.
Cell line：Cervical cancer tumer line Hela, lung adenocarcinoma cell line A549 and breast cancer cell line MCF-7 are (Central-South big
Xue Xiangya medical colleges cell bank is provided).
Reagent：Tetrazolium bromide (MTT), RPMI RPMI-1640s, NBCS, antibiotic (U.S.'s hero's life
Technology company)；Pancreatin (AMRESCO companies of the U.S.)；96 well culture plates (hero Life Technologies, Inc. of the U.S.)；Diformazan
Base sulfoxide (Sigma Co., USA).
Instrument：HFsafe-1500 types superclean bench, HF151UV types CO2(Shanghai power Shen scientific instrument have incubator
Limit company)；XSP-15C types inverted microscope (the rectangular optical instrument Co., Ltd in Shanghai)；Multiskan MK3 type enzyme marks
Instrument (Thermo companies of the U.S.)；Ultra-pure water preparing instrument (Milli-Q companies of the U.S.).
Experimental implementation：Test of the sample to Hela cells, A549 cells and MCF-7 cells.The experiment behaviour of every kind of cell
Make process identical, in an experimentation, per sample (p.s.) sets 5 concentration gradients (0.010 μm of ol/mL, 0.030
μm ol/mL, 0.100 μm of ol/mL, 0.300 μm of ol/mL and 1.000 μm of ol/mL), four parallel samples of each concentration,
Parallel 3 times of every group of experiment, and compareed by blank group and draw a conclusion.ELIASA detects each hole OD values, Detection wavelength 570nm.
3. antitumor activity evaluation
(1) cell inhibitory rate is calculated：
(2)IC50Value is calculated
Sample solution concentration logarithm value and cell inhibitory rate linear regression, half-inhibition concentration of the sample to cell is calculated using software
IC50Value.IC of the preferred compound to Hela cells, A549 cells and MCF-7 cells50It is shown in Table 1~3.
Inhibitory activity of the 5- piperonyls thiazole of table 1 to Hela cells
| 5- piperonyl thiazoles | IC50, μm ol/L |
| 5- piperonyl -4- the tert-butyl groups -2- (3- chloroanilinos) thiazole | 8.27±0.89 |
| 5- piperonyl -4- the tert-butyl groups -2- (3- bromoanilinos) thiazole | 6.43±3.02 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- nitrobenzene amino) thiazole | 4.15±0.01 |
| 5- piperonyl -4- the tert-butyl groups -2- (3,4- dichloro-benzenes amino) thiazole | 7.83±2.17 |
| 5- piperonyl -4- the tert-butyl groups -2- (3,5- dichloro-benzenes amino) thiazole | 5.80±0.59 |
| 5- piperonyl -4- the tert-butyl groups -2- (the fluoro- 3- chloroanilinos of 4-) thiazole | 4.60±0.52 |
| 5- piperonyl -4- the tert-butyl groups -2- [3,5- bis- (trifluoromethyl) phenylamino] thiazole | 2.07±0.88 |
Inhibitory activity of the 5- piperonyls thiazole of table 2 to A549 cells
| 5- piperonyl thiazoles | IC50, μm ol/L |
| 5- piperonyl -4- the tert-butyl groups -2- (2- fluoroanilinos) thiazole | 7.57±0.22 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- fluoroanilinos) thiazole | 5.81±0.27 |
| 5- piperonyl -4- the tert-butyl groups -2- (2- chloroanilinos) thiazole | 6.84±0.21 |
| 5- piperonyl -4- the tert-butyl groups -2- (3- chloroanilinos) thiazole | 2.06±0.09 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- chloroanilinos) thiazole | 9.19±1.03 |
| 5- piperonyl -4- the tert-butyl groups -2- (3- bromoanilinos) thiazole | 5.00±0.94 |
| 5- piperonyl -4- the tert-butyl groups -2- [4- (trifluoromethyl) phenylamino] thiazole | 9.22±1.64 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- nitrobenzene amino) thiazole | 8.26±0.18 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- ethoxycarbonyls phenylamino) thiazole | 8.51±4.30 |
| 5- piperonyl -4- the tert-butyl groups -2- [3,5- bis- (trifluoromethyl) phenylamino] thiazole | 3.52±0.49 |
Inhibitory activity of the 5- piperonyls thiazole of table 3 to MCF-7 cells
| 5- piperonyl thiazoles | IC50, μm ol/L |
| 5- piperonyl -4- the tert-butyl groups -2- (3- methylphenylaminos) thiazole | 4.91±0.03 |
| 5- piperonyl -4- the tert-butyl groups -2- (2- fluoroanilinos) thiazole | 4.49±0.49 |
| 5- piperonyl -4- the tert-butyl groups -2- (2- chloroanilinos) thiazole | 8.99±0.97 |
| 5- piperonyl -4- the tert-butyl groups -2- (3- chloroanilinos) thiazole | 3.00±0.25 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- chloroanilinos) thiazole | 3.48±0.12 |
| 5- piperonyl -4- the tert-butyl groups -2- (3- bromoanilinos) thiazole | 4.66±0.25 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- bromoanilinos) thiazole | 4.71±0.81 |
| 5- piperonyl -4- the tert-butyl groups -2- [3- (trifluoromethyl) phenylamino] thiazole | 3.32±0.31 |
| 5- piperonyl -4- the tert-butyl groups -2- [4- (trifluoromethyl) phenylamino] thiazole | 3.54±1.90 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- methoxybenzenes amino) thiazole | 9.36±1.68 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- nitrobenzene amino) thiazole | 2.55±0.34 |
| 5- piperonyl -4- the tert-butyl groups -2- (4- ethoxycarbonyls phenylamino) thiazole | 5.95±0.37 |
| 5- piperonyl -4- the tert-butyl groups -2- (the fluoro- 3- chloroanilinos of 4-) thiazole | 8.66±0.38 |
| 5- piperonyl -4- the tert-butyl groups -2- [3,5- bis- (trifluoromethyl) phenylamino] thiazole | 9.03±0.96 |
Active testing result shows that 5- piperonyls thiazole or its salt are to cervical cancer cell (Hela cells), people's lung gland
Cancer cell (A549 cells) and human breast cancer cell (MCF-7 cells) have good inhibitory activity, can be used to prepare
Antineoplastic.
Claims (2)
1. application of the 5- piperonyls thiazole or its salt shown in chemical structural formula I in cancer therapy drug is prepared：
Wherein, R is selected from：C1~C2Alkyl；C3~C4Straight chained alkyl or C3~C4Branched alkyl；X1、X5It is selected from：Hydrogen,
Deuterium, C1~C2Alkyl, fluorine, chlorine, bromine or nitro；X2、X4It is selected from：Hydrogen, deuterium, C1~C2Alkyl, fluorine, chlorine, bromine,
Nitro or trifluoromethyl；X3It is selected from：Hydrogen, deuterium, C1~C2Alkyl, methoxyl group, ethyoxyl, fluorine, chlorine, bromine, nitro,
Ethoxycarbonyl or trifluoromethyl；The salt is selected from：Hydrochloride, hydrobromate, sulfate, nitrate, phosphate, first
Sulfonate, benzene sulfonate, tosilate, malate, lactate, succinate, maleate or fumarate.
2. the application described in claim 1, the 5- piperonyl thiazoles wherein shown in formula I are selected from：5- piperonyls -4-
The tert-butyl group -2- (3- methylphenylaminos) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (2- fluoroanilinos) thiazole, 5- piperonyls -4-
The tert-butyl group -2- (4- fluoroanilinos) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (2- chloroanilinos) thiazole, 5- piperonyls -4-
The tert-butyl group -2- (3- chloroanilinos) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (4- chloroanilinos) thiazole, 5- piperonyls -4-
The tert-butyl group -2- (3- bromoanilinos) thiazole, 5- the piperonyl -4- tert-butyl groups -2- (4- bromoanilinos) thiazole, 5- piperonyls -4-
The tert-butyl group -2- [3- (trifluoromethyl) phenylamino] thiazole, the 5- piperonyl -4- tert-butyl groups -2- [4- (trifluoromethyl) phenylamino] thiophene
Azoles, the 5- piperonyl -4- tert-butyl groups -2- (4- methoxybenzenes amino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (4- nitrobenzene amino)
Thiazole, the 5- piperonyl -4- tert-butyl groups -2- (4- ethoxycarbonyls phenylamino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (3,4-
Dichloro-benzenes amino) thiazole, the 5- piperonyl -4- tert-butyl groups -2- (3,5- dichloro-benzenes amino) thiazole, the 5- piperonyl -4- tert-butyl groups
- 2- (the fluoro- 3- chloroanilinos of 4-) thiazoles or the 5- piperonyl -4- tert-butyl groups -2- [3,5- bis- (trifluoromethyl) phenylamino] thiazole.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1897814A (en) * | 2003-12-24 | 2007-01-17 | 拜尔作物科学有限公司 | Plant growth regulation |
| US20120172374A1 (en) * | 2010-12-29 | 2012-07-05 | Development Center For Biotechnology | Novel tubulin inhibitors and methods of using the same |
| CN104530035A (en) * | 2015-01-07 | 2015-04-22 | 湖南大学 | 5-piperonyl-4-alkyl-2-aromatic aminothiazole and preparing method and application thereof |
| CN104530036A (en) * | 2015-01-07 | 2015-04-22 | 湖南大学 | 5-piperonyl-4-alkyl-2-benzyliminothiazole and preparing method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1897814A (en) * | 2003-12-24 | 2007-01-17 | 拜尔作物科学有限公司 | Plant growth regulation |
| US20120172374A1 (en) * | 2010-12-29 | 2012-07-05 | Development Center For Biotechnology | Novel tubulin inhibitors and methods of using the same |
| CN104530035A (en) * | 2015-01-07 | 2015-04-22 | 湖南大学 | 5-piperonyl-4-alkyl-2-aromatic aminothiazole and preparing method and application thereof |
| CN104530036A (en) * | 2015-01-07 | 2015-04-22 | 湖南大学 | 5-piperonyl-4-alkyl-2-benzyliminothiazole and preparing method and application thereof |
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